1. Field of the Invention
The present invention concerns a process for the conversion of (2S,3S)-2-amino-3-phenyl-1,3-propanediols into their corresponding (2R,3R)-enantiomers.
2. Discussion of the Background
Many 2-amino-3-phenyl-1,3-propanediols are useful as intermediates for the synthesis of antibiotics like Chloramphenicol (Merck Index, X Ed., No. 2035, page 289) and Thiamphenicol (Merck Index, X Ed., No. 9140, page 1332). Often, their synthesis is accompanied with discard products having a wrong configuration.
Said compounds may be collected under the following formula ##STR1## wherein X=H, NO.sub.2, CH.sub.3 S, CH.sub.3 SO or CH.sub.3 SO.sub.2.
The compounds of formula I having the (2R,3R) configuration are useful for the synthesis of the above cited antibiotics while the enantiomers I (2S,3S) are generally discard products of the industrial synthesis.
The compounds of formula I wherein X=NO.sub.2 are known as threo-(2R,3R)-micamine and (2S,3S)-micamine while those in which X=CH.sub.3 S as threo-(2R,3R)-thiomicamine and (2S,3S)-thiomicamine.
A further compound under development having antibiotic activity is Florfenicol (European Patent No. 14437--Schering Co.) which has a structure analogous to that of Thiamphenicol wherein instead of the primary hydroxy group there is a fluorine atom.
The synthesis of Florfenicol, (2S,3R)-3-(4-methylsulphonylphenyl)-3-hydroxy-2-dichloroacetamido-1-fluoro -propane, may be carried out starting from (2R,3R)-thiomicamine (see also European Patent application No. 130,633--Zambon S.p.A.).
Some of the processes for the synthesis of Chloramphenicol or Thiamphenicol comprise the preparation of a racemic mixture of the isomers threo (2R,3R)+(2S,3S) of micamine or of thiomicamine.
The desired threo (2R,3R) isomer is then separated by resolution process and is converted into the antibiotic compound by N-dichloroacetylation and, in the case of Thiamphenicol, also by oxidation of the CH.sub.3 S group into CH.sub.3 SO.sub.2.
The isomer threo-(2S,3S), on the contrary, is a discard product of the synthesis which must be eliminated thus increasing the cost of the desired isomer.
Some processes have been studied which allow the racemization of the (2S,3S)-intermediate, i.e. to convert them into a 1:1 mixture of the threo (2R,3R) and (2S,3S)-isomers [Tetrahedron Letters, 29, 5561, (1988) and references cited therein].
From these racemates the (2R,3R)-isomer must be separated and the (2S,3S)-isomer must be racemized again.
The process for racemization of aminodiols thus becomes cumbersome. So, it would be useful to have available a process allowing the stereochemical inversion of the discard products of the synthesis of Chloramphenicol and Thiamphenicol, by transforming directly the above reported intermediates (formula I) having (2S,3S)-configuration into their (2R,3R) enantiomers useful for the synthesis of the compounds having antibiotic activity.
However, to our knowledge, there has never been previously described a process allowing said double inversion.